A Tumor-Specific Cascade Amplification Drug Release Nanoparticle for Overcoming Multidrug Resistance in Cancers

Mingzhou Ye; Yuxin Han; Jianbin Tang; Ying Piao; Xiangrui Liu; Zhuxian Zhou; Jianqing Gao; Jianghong Rao; Youqing Shen

doi:10.1002/adma.201702342

A Tumor-Specific Cascade Amplification Drug Release Nanoparticle for Overcoming Multidrug Resistance in Cancers

Adv Mater. 2017 Oct;29(38). doi: 10.1002/adma.201702342. Epub 2017 Aug 21.

Authors

Mingzhou Ye^{1

2}, Yuxin Han¹, Jianbin Tang¹, Ying Piao¹, Xiangrui Liu¹, Zhuxian Zhou¹, Jianqing Gao², Jianghong Rao³, Youqing Shen¹

Affiliations

¹ Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China.
² Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
³ Molecular Imaging Program at Stanford Department of Radiology, School of Medicine, Stanford University, CA, 94305, USA.

PMID: 28833669
DOI: 10.1002/adma.201702342

Abstract

A cascade amplification release nanoparticle (CARN) is constructed by the coencapsulation of β-lapachone and a reactive-oxygen-species (ROS)-responsive doxorubicin (DOX) prodrug, BDOX, in polymeric nanoparticles. Releasing β-lapachone first from the CARNs selectively increases the ROS level in cancer cells via NAD(P)H:quinone oxidoreductase-1 (NQO1) catalysis, which induces the cascade amplification release of DOX and overcomes multidrug resistance (MDR) in cancer cells, producing a remarkably improved therapeutic efficacy against MDR tumors with minimal side effects.

Keywords: anticancer prodrug; cascade amplification drug release; drug delivery; multidrug resistance; β-lapachone.

MeSH terms

Cell Line, Tumor
Doxorubicin
Drug Liberation
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Humans
Nanoparticles*
Prodrugs

Substances

Prodrugs
Doxorubicin

Grants and funding

R01 DK099800/DK/NIDDK NIH HHS/United States